Modulation of neuronal nicotinic acetylcholine receptors by glucocorticoids.
Abstract
AIM: To investigate the nongenomic effect of the glucocorticoid corticosterone on
nicotinic acetylcholine receptor (nAChR) in PC12 cells.
METHODS: The acetylcholine (ACh)-induced current was measured on nerve growth
factor differentiated PC12 cells using whole-cell patch-clamp techniques.
RESULTS: The ACh-induced current (IACh) proved to be generated through neuronal
nAChR. When ACh (30 micromol/L) was applied simultaneously with corticosterone
(0.1 - 10 micromol/L), the decay of IACh was faster with slight inhibition on the
peak current amplitude. Pretreating PC12 cells with corticosterone augmented the
inhibition on the peak IACh and did not alter receptor desensitization. Bovine
serum albumin-conjugated corticosterone (0.1 - 10 micromol/L) had the inhibition
similar to corticosterone. The rapid effect induced by corticosterone was
reversible, concentration-dependent, and voltage-independent.
CONCLUSION: Corticosterone has rapid inhibitory effect on IACh, which is mediated
by a nongenomic mechanism. It indicates that corticosterone binds to the specific
site on the outer cell membrane, probably on the neuronal nicotinic
receptor-coupled channel, and inhibits the IACh in a noncompetitive manner, thus
controlling the immediate catecholamine release from the sympathetic cells.
Keywords:
nicotinic acetylcholine receptor (nAChR) in PC12 cells.
METHODS: The acetylcholine (ACh)-induced current was measured on nerve growth
factor differentiated PC12 cells using whole-cell patch-clamp techniques.
RESULTS: The ACh-induced current (IACh) proved to be generated through neuronal
nAChR. When ACh (30 micromol/L) was applied simultaneously with corticosterone
(0.1 - 10 micromol/L), the decay of IACh was faster with slight inhibition on the
peak current amplitude. Pretreating PC12 cells with corticosterone augmented the
inhibition on the peak IACh and did not alter receptor desensitization. Bovine
serum albumin-conjugated corticosterone (0.1 - 10 micromol/L) had the inhibition
similar to corticosterone. The rapid effect induced by corticosterone was
reversible, concentration-dependent, and voltage-independent.
CONCLUSION: Corticosterone has rapid inhibitory effect on IACh, which is mediated
by a nongenomic mechanism. It indicates that corticosterone binds to the specific
site on the outer cell membrane, probably on the neuronal nicotinic
receptor-coupled channel, and inhibits the IACh in a noncompetitive manner, thus
controlling the immediate catecholamine release from the sympathetic cells.